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Expert Opin Biol Ther. 2010 Apr;10(4):547-62. doi: 10.1517/14712591003614756.

T cell receptor (TCR) gene therapy to treat melanoma: lessons from clinical and preclinical studies.

Author information

1
Erasmus MC-Daniel den Hoed Cancer Center, Laboratory of Experimental Tumor immunology, Rotterdam, The Netherlands.

Abstract

IMPORTANCE OF THE FIELD:

Adoptive T cell therapy (ACT) with tumour infiltrating lymphocytes is currently the best treatment option for metastatic melanoma. Despite its clinical successes, ACT has limitations in availability and generation of therapeutic T cells for a larger group of patients. Introduction of tumour-specific T cell receptors into T cells, termed TCR gene therapy, can provide an alternative for ACT that is more widely applicable and might be extended to other types of cancer.

AREAS COVERED IN THIS REVIEW:

The current status of TCR gene therapy studies including clinical challenges, such as on-target toxicity, compromised anti-tumour T cell responses, compromised T cell persistence and potential immunogenicity of receptor transgenes. Strategies to address these challenges are covered.

WHAT THE READER WILL GAIN:

A listing and discussion of strategies that aim at improving the efficacy and safety of TCR gene therapy. Such strategies address antigen choice, TCR mis-pairing, functional avidity and persistence of T cells, immune responses towards receptor transgenes, and combination of ACT with other therapies.

TAKE HOME MESSAGE:

To ensure further clinical development of TCR gene therapy, it is necessary to choose safe T cell target antigens, and implement (combinations of) strategies that enhance the correct pairing of TCR transgenes and the functional avidity and persistence of T cells.

PMID:
20146634
DOI:
10.1517/14712591003614756
[Indexed for MEDLINE]

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